The present invention relates to a new composition and the use thereof.
In a preferred embodiment form of the present invention there is an active ingredient poorly soluble in water. Cyclosporins are an example of such poorly soluble active ingredients.
Cyclosporins comprise a class of cyclic poly-N-methylated undecapeptides, whose representatives have pharmacological properties, in particular immuno-suppressive, anti-inflammatoric and/or anti-parasitic properties. The most famous of representatives of this class is cyclosporin A which is the active ingredient of the commercially available preparations SANDIMMUN and NEORAL.
Cyclosporins are neutral lipophilic (i.e. hydrophobic) substances with a low water solubility. Formulations of cyclosporins, e.g. for oral administration, are based mainly on the use of ethanol and oils or similar auxiliary agents as carrier media. Thus according to the Journal of Drug Targeting, 1998, Vol. 5, No. 6, pages 443-458 (in particular pages 447 and 448) the commercially available preparation SANDIMMUN is obtainable in three different forms, specifically
soft gelatine capsules, containing cylcosporine A, water-free ethyl alcohol (up to 12.7%), Labrafil M 2125 CS (polyoxyethylated glycolisated glycerides), maize oil and further ingredients;
an oral solution, containing cyclosporin A, ethyl alcohol (up to 12.5%), olive oil, Labrafil M 1944 CS (polyoxyethylated oleic acid glyceride); and further ingredients; and
an injection preparation, containing cyclosporin A, ethyl alcohol (32.9%) and Cremophor EL (polyethoxylated risinus oil); and the commercially available preparation NEORAL in two forms, specifically
soft gelatine capsules, containing cyclosporin A, water-free ethyl alcohol (up to 9.5%), maize oil glycerides, Cremophor RH 40 (polyoxyethylated hydrated risinus oil), propylene glycol and further ingredients; and
an oral solution, containing cyclosporin A, water-free ethyl alcohol (up to 9.5%), maize oil glycerides, Cremophor RH 40, propylene glycol and further excipients.
From DE 39 30 928 C2 there are known formulations which contain a cyclosporin as an active ingredient; a hydrophilic phase, specifically a pharmaceutically acceptable C1-C5-alkyl- or tetrahydrofurfuryl-diether or -partial ether of a low-molecular mono- or polyoxy-C2-C12-alkanediol, preferably transcutol (diethylene glycol mono ethyl ether) or glycofurol(tetrahydrofufurylalcohol polyethylene glycol ether) and/or 1,2-propylene glycol; a lipophilic phase; and a surface-active agent. The hydrophilic phase may additionally also contain further components, for example lower alkanols, such as ethanol.
From WO 99/00002 A there are known formulations which contain cyclosporin as an active ingredient; a polycarboxylic acid ester and/or a polyolcarboxylic acid ester; an oil; and a surface-active agent. The polycarboxylic acid esters are hereby esterification products of polycarboxylic acids with 2-10, preferably 3-5 carboxyl groups with C1-C10 alcohols, such as triethyl citrate, tributyl citrate, acetyltributyl citrate and acetyltriethyl citrate, and the polyolcarboxylic acids are hereby esterification products of polyols with 2-10, preferably 3-5 hydroxyl groups with C2-C11-carboxylic acids, such as e.g. triacetine.